The proposed study will help elucidate the sequence specific conformation changes undergone by DNA. Although different conformations within DNA have been observed for different sequences and although conformation transitions within DNA as a function of counterion type and concentration have been monitored, little is known about conformation changes induced in different sequences. Such specific inducible conformation changes could be the basis for highly specific recognition processes involved in gene expression. The influence of methylation of DNA-cytosine on the inducible conformations may provide a way of altering the recognition process and so be important in differentiation and expression. Current evidence suggests that this mechanism may be operative in CpG sequences of neoplastic cells. We propose to conduct a theoretical study of the conformation transitions which can be induced by polyamines, metal cations and the basic residues of proteins. We have already shown that interaction of the amine groups of proflavin with the backbone phosphate can induce structural transitions required for the intercalation of proflavin into CpG sequences. We have further shown that the sequence specificity of the binding of ethidium to DNA results from specific structural transitions which are much more easily accomplished by those sequences which bind ethidium most readily. In order to perform the required calculations of the conformations induced in different base sequences, a refinement of both quantum chemical and empirical potential function approaches is proposed. The refinements will allow the effect of solvent activity and counterion type to be included in a meaningful way. By careful comparison of the results with existing spectroscopic data on conformation transitions and on base sequence specific conformations, the reliability of the results can be monitored.